ESPE Abstracts (2019) 92 P1-173

Cutoff Value for 25 Hydroxy-Vitamin D Which Leading to sYmptomatic Vitamin D Deficiency in Children is 15 ng/mL in a Chemiluminescent Immunoassay

Yasuko Ogiwara1, Rumi Hachiya1, Nao Shibata2, Akira Ishii3, Shinji Higuchi4, Keisuke Nagasaki3, Hotaka Kamasaki4, Toru Yorifuji4, Yukihiro Hasegawa1


1Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 2Niigata University Medical & Dental Hospital, Niigata, Japan. 3Sapporo Medical University Hospital, Sapporo, Japan. 4Osaka City General Hospital, Osaka, Japan


Background & Purpose: Vitamin D is essential for bone and calcium metabolism, and a deficiency of this nutrient can lead to rickets and hypocalcemia. A 25 hydroxy-vitamin D (25OHD) value below 12 ng/mL (30 nmol/L) has been established by global consensus on the basis of several studies as constituting vitamin D deficiency. For example, (1) the incidence of nutritional rickets can increase at a 25OHD concentration of less than 12 ng/mL; (2) PTH increases when the 25OHD level is below 13.6 ng/mL, etc. No studies have yet analyzed the association between the 25OHD value and the occurrence of rickets and hypocalcemia due to vitamin D deficiency. We herein aimed to examine the association between 25OHD levels and the symptoms of vitamin D deficiency by receiver operation characteristic (ROC) analysis.

Method: We conducted a retrospective study from April 2013 to March 2018 at four hospitals. All subjects aged 0 to 15 years who were screened for vitamin D deficiency were recruited.

Results: Chemiluminescent immunoassay (CLIA) was used to measure the 25OHD levels in 605 subjects. Of these, 408 subjects were excluded due to having a cause of rickets or hypocalcemia other than vitamin D deficiency or for having already received treatment. As a result, 197 subjects (92 males) ranging in age from 0.1~14.8 years were analyzed. Of these, 117 (59.4%) were asymptomatic, 11 (5.6%) had healing rickets, and 69 (35.0%) were symptomatic (had received the diagnosis of rickets or hypocalcemia). The 11 patients with healing rickets were excluded from the analysis.

First, ROC analysis was performed. The cut-off value for 25OHD for the asymptomatic group (n=117) and symptomatic group (n=69) was 15.0 ng/mL, and the sensitivity and specificity was 73% and 99%, respectively (AUC: 0.880, 95% CI: 0.831-0.929).

Next, a sub-analysis of ROC was done due to a statistical difference in the U-Ca/Cr levels between the asymptomatic and symptomatic groups. When the 25OHD value was calculated separately for subjects with U-Ca/Cr≧0.1 (n=50) and <0.1 (n=78), the cut-off value of 25OHD, similarly obtained, was 15.0 ng/mL and 9.3 ng/mL, respectively.

Discussion & Conclusion: Our study found that the 25OHD cutoff value leading to symptomatic vitamin D deficiency was 15 ng/mL on CLIA. The findings suggest that low U-Ca/Cr, which may reflect Ca intake, modifies the manifestation of rickets and hypocalcemia.